Disclosed are a substituted pyrimidine piperazine compound of Formula (I), or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and a pharmaceutical composition comprising the compound thereof. The substituted pyrimidine piperazine compound and the pharmaceutical composition disclosed herein can be used to inhibit 5-hydroxytryptamine reuptake and/or activate the 5-HT